Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Woischke, C; Schaaf, CW; Yang, HM; Vieth, M; Veits, L; Geddert, H; Märkl, B; Stömmer, P; Schaeffer, DF; Frölich, M; Blum, H; Vosberg, S; Greif, PA; Jung, A; Kirchner, T; Horst, D.
In-depth mutational analyses of colorectal neuroendocrine carcinomas with adenoma or adenocarcinoma components.
Mod Pathol. 2017; 30(1): 95-103.
Doi: 10.1038/modpathol.2016.150
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Vosberg Sebastian
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- Abstract:
- Neuroendocrine carcinomas (NECs) of the colorectum are rare but highly aggressive neoplasms. These tumors show some shared genetic alterations with colorectal adenocarcinomas, and most of them have adjacent glandular adenoma or adenocarcinoma components. However, genetic data on colorectal NECs still are sparse and insufficient for definite conclusions regarding their molecular origin. Based on morphological characterization, panel and whole-exome sequencing, we here present results from an in-depth analysis of a collection of 15 colorectal NECs with glandular components, 10 of which by definition were mixed adenoneuroendocrine carcinomas (MANECs). Among shared genetic alterations of both tumor components, we most frequently found TP53, KRAS and APC mutations that also had highest allele frequencies. Mutations exclusive to glandular or neuroendocrine components outnumbered shared mutations but occurred at lower allele frequencies. Our findings not only provide additional evidence for a common clonal origin of colorectal NECs and adjacent glandular tumor components, but strongly suggest their development through the classical adenoma-carcinoma sequence. Moreover, our data imply early separation of glandular and neuroendocrine components during malignant transformation with subsequent independent mutational evolution.
- Find related publications in this database (using NLM MeSH Indexing)
- Adenocarcinoma - genetics
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- Adenomatous Polyposis Coli Protein - genetics
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- Alleles -
- Carcinoma, Neuroendocrine - genetics
- Carcinoma, Neuroendocrine - pathology
- Colorectal Neoplasms - genetics
- Colorectal Neoplasms - pathology
- DNA Mutational Analysis -
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- Gene Frequency -
- Humans -
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- Middle Aged -
- Mutation -
- Proto-Oncogene Proteins p21(ras) - genetics
- Tumor Suppressor Protein p53 - genetics
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